The prolactin receptor (PRLR) is a class I cytokine receptor with single membrane-domain, possesses 4 cysteines in the N-terminal region of the extracellular domain that are critical to keep the structural and functional integrity of the PRL-receptor. Prolactin (PRL), growth hormone (GH), and prolactin lactogen (PL) interact with PRLR homodimers and activates several signaling pathways, such as STAT5 and ERK1/2. The best known function for PRL/PRLR complex is to stimulate mammary gland to enable female mammals to produce milk. The PRL/PRLR complex play key roles in different physiological process such as: regulation of immune functions, pancreatic development, angiogenesis, reproduction, osmoregulation, and metabolism. The PL/PRLR complex is involved in the regression of angiogenesis during luteolysis; thus genetic ablation of the prolactin receptor contributed to angiogenesis defects in the corpus luteum in mice. The expression of prolactin receptor has been reported in rheumatoid arthritis and psoriatic arthritis synovial tissue and it has been suggested that contributes to macrophage activation. In addition, synovial-tissue PRL mRNA expression has been measured by quantitative PCR in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and the expression correlated significantly with clinical disease parameters in those patients.